Determining the mechanisms of normal cell cycle control is critical for our understanding of both development and oncogenesis. During development, cell proliferation occurs by coordinating progress through the cell cycle with growth. Conversely, cell cycle arrest occurs prior to, and is often necessary for, terminal differentiation. Cell proliferation and cell cycle arrest are also highly regulated after the completion of development: stem cells in adult tissues are under tight cell cycle control, as are quiescent cells that only proliferate in response to particular stimuli. Breakdowns in cell cycle control in any of these circumstances can have drastic consequences and contribute to the deregulated growth typical of cancer. The long term objective of this project is to elucidate how developmental programs affect cell cycle progression, a process that remains poorly understood. In this proposal we focus on gene expression mechanisms that control the G1-S transition because this is when most cells decide whether to enter or to exit the cell cycle. PUBLIC HEALTH RELEVANCE: Cell proliferation is a fundamental aspect of the biology of all organisms, and is controlled by a highly orchestrated series of cell biological events termed the cell cycle that directs the accurate duplication and inheritance of the genome. A detailed molecular description of cell cycle events during animal development is critical for our understanding of cell proliferation control, and how such control goes awry in diseases like cancer.